Do live birth rate and obstetric outcomes vary between immediate and delayed embryo transfers following freeze-all cycles?

RESEARCH QUESTION: Do live birth rates (LBR), obstetric and perinatal outcomes vary between women who underwent frozen embryo transfer (ET) in the immediately subsequent menstrual cycle, and with those who underwent delayed frozen ET. DESIGN: Retrospective cohort study (n = 198) consisting of 119 women who underwent immediate transfer within 30 days of oocyte retrieval (OR) and 79 women who underwent delayed transfer which was performed after >30 days following OR. Either flexible antagonist or flexible progestin-primed ovarian stimulation protocols were started after a baseline ultrasonography on the second or third day of menstrual cycle. Only freeze all cycles were included in the study and all transfers were with hormonal endometrial preparation. Main outcome measures were LBR, birth weight, gestational day at birth and pregnancy complications. RESULTS: Peak estradiol level on trigger day (2746 vs 2081 pg/ml) and number of metaphase-two oocytes (13 vs 10) were significantly higher in the immediate transfer group. Clinical pregnancy rate per ET was similar between the groups (50.4% vs 44.3%). However, miscarriage rate per positive pregnancy was significantly higher (12.3% vs 31.1%) while LBR per ET was significantly lower (42.9% vs 26.6%) in the delayed transfer group. Median gestational age at delivery were 267.5 and 268 days in the immediate and delayed transfer groups. Median birthweight was significantly higher in the delayed transfer group (3520 vs 3195 g). Adjusted analyses also suggest similar LBR with immediate and delayed transfer. CONCLUSION(S): Frozen ET in the immediate menstrual cycle and delayed ET, after a freeze all strategy did not show significant difference in terms of LBR after adjustment. Obstetric and perinatal outcomes of frozen ET in the immediate menstrual cycle appear reassuring.

Pharmacovigilance study of a regional intravenous immunoglobulin (II): evaluation and comparison of an improved pharmaceutical form / Estudio de farmacovigilancia de una inmunoglobulina intravenosa regional (II): evaluación y comparación de una forma farmacológica mejorada

Introduction: Intravenous immunoglobulin (IVIG) therapy is an effective treatment in patients with different diseases. This product must comply with all the regulatory requirements established by the World Health Organization and the European Pharmacopoeia for clinical tolerance, therapeutic efficacy, and viral safety. Although IVIG are effective and safe products, in some patients they may cause adverse reactions. Objectives: The aim of this study was to assess the clinical tolerance of two pharmaceutical forms (lyophilized and liquid) of Imunoglobulina G Endovenosa UNC® (IVIG UNC®), a regional IVIG preparation, and to compare the reported data. Patients and methods: The pharmacovigilance reports of 149 infusions in 51 patients treated with lyophilized IVIG UNC® and of 157 infusions in 53 patients treated with liquid IVIG UNC® were statistically evaluated. Clinical tolerance was evaluated through the adverse reactions reported. Results: Lyophilized IVIG UNC®: adverse reactions were reported in 6.7 % of the total number of infusions. Of these reactions, 4.0 % were mild, 2.0 % were moderate, and 0.7 % severe. Liquid IVIG UNC®: adverse reactions were reported in 3.2 % of the total number of infusions; of these, 1.3 % were mild, 1.9 % were moderate, and 0.0 % were severe. Statistical analysis showed no association between tolerance and the pharmaceutical form used (p > 0.05) and indicated similar tolerance for both preparations. Conclusions: Based on the results obtained, the excellent clinical tolerance of both pharmaceutical forms of IVIG UNC® can be confirmed

Introducción: La administración de inmunoglobulina endovenosa (IGEV) es una terapéutica eficaz en pacientes con diversas patologías. Este medicamento debe cumplir con todos los requerimientos reguladores establecidos por la Organización Mundial de la Salud (OMS) y la Farmacopea Europea (FE) en cuanto a tolerancia clínica, eficacia terapéutica y seguridad viral. Aunque las IGEV son productos eficaces y seguros, en algunos pacientes pueden provocar reacciones adversas. Objetivos: El objetivo de este trabajo fue evaluar la tolerancia clínica de dos formas farmacéuticas (liofilizada y líquida) de Inmunoglobulina G Endovenosa UNC® (IGEV UNC®), una IGEV regional, y comparar los datos reportados. Pacientes y métodos: Se evaluaron estadísticamente los Registros de Farmacovigilancia de 149 infusiones administradas a 51 pacientes tratados con IGEV UNC® liofilizada y 157 infusiones administradas a 53 pacientes con IGEV UNC® líquida. La tolerancia clínica se evaluó considerando las reacciones adversas reportadas. Resultados: IGEV UNC® liofilizada: Se informaron reacciones adversas en 6,7% de las infusiones administradas, de las cuales 4,0% fueron leves, 2,0% moderadas y 0,7% graves. IGEV UNC® líquida: Se informaron reacciones adversas en 3,2% de las infusiones administradas, de las cuales 1,3% fueron leves, 1,9% moderadas y 0,0% graves. El análisis estadístico no mostró asociación entre tolerancia y forma farmacéutica empleada (p>0,05) indicando una tolerancia similar para ambas preparaciones. Conclusiones: Los resultados obtenidos permiten confirmar la excelente tolerancia clínica de ambas formas farmacéuticas de IGEV UNC®

The effect of cryoprotectants on the physical properties of large liposomes containing sodium diclofenac.

Large liposomes (1-10 microm) containing sodium diclofenac were prepared and lyophilized using lactose or mannitol (7.5% in respect to the lipid content) as cryoprotectants. The physical studies of liposomes were performed during 30 days of storage in a dry or resuspended form. Lyophilization of large liposomes and storage in the dry form at 5 degrees C increases their physical stability. Lactose is a cryoprotectant which does not influence changes of properties of liposomes regarding their size, encapsulation efficacy and release rate. Large liposomes lyophilized in the presence of mannitol tend to increase in size and encapsulation efficacy, but the lipid bilayers are stabilized and less permeable to the drug.

Investigation of protein/carbohydrate interactions in the dried state. 1. Calorimetric studies.

Isoperibol calorimetry was used to evaluate protein/carbohydrate interactions after freeze drying. rh-DNase, rh-GH, rh-MetGH, and rh-IGF-I were freeze dried with either mannitol, sucrose, trehalose, or dextran at concentrations ranging from 0% to 100% (w/w). Enthalpies of solution for both freeze-dried and physical mixtures were measured in water at 25 degrees C. Differential scanning calorimetry was used to monitor changes in the melting or crystallization temperatures of the lyoprotectants. Linear relationships between enthalpies of solution and the percentage of protein in the formulations were observed for all physical mixtures. In contrast, nonlinear relationships between the enthalpies of solution and protein content were observed for the freeze-dried mixtures. Mannitol-containing mixtures were characterized by negative deviation from linearity, while positive deviations were detected for mixtures containing sucrose or trehalose. Using DSC, sucrose was found to be amorphous at low and not detected at high protein content in the freeze-dried mixtures. Melting of mannitol was observed through almost all of the protein concentration range examined. Two melting endotherms, however, were observed for mannitol at most protein/mannitol ratios, indicating the presence of protein/mannitol interactions. This work suggests that direct interactions occur between proteins and carbohydrates in lyophilized mixtures.

Vial lyophilization: calculations on rate limitation during primary drying.

PURPOSE: The aim of this study was to assess the rate limiting factors in the sublimation phase of freeze drying and to propose a simple model on the basis of these rate limitations. METHODS: A programmable freeze dryer was used. The load consisted of vials of varying size and various contents. To increase heat transfer, conductive paste was applied while the resistance toward mass transport was varied by using different restrictive capillaries. RESULTS: It was found that heat transfer limits the rate of sublimation. Presence of the commonly used excipient mannitol did not have a consequence on the rate of sublimation. The same applied for the restrictions towards mass transport. It was found that there exists not only a barrier against heat transport under the vial, but also between the glass wall and the frozen solution. CONCLUSIONS: From the results, a set of equations is proposed that enables to predict optimum sublimation conditions. For the pharmaceutical technologist this can serve as a simple and useful tool to derive a suitable freeze drying program.

Development of cycles for lyophilization.

In order to find the freeze-drying cycle for the effective drying of a given biological entity or a material of biologic origin by sublimation of ice in vacuo, numerous time-consuming, trial and error preliminary studies have been required. Following a series of studies using different shelf temperatures, -30 degrees, -10 degrees, 0 degrees, +10 degrees and +20 degrees C, and elapsed times of 1,500, 2,000, 2,700, 4,000 and 5,500 minutes, plug characteristics and contents of residual moistures of freeze-dried 3 ml samples of 2% serum albumin were determined. Using the statistical method of least squares, geometric curves were fitted to the plot of times versus residual moistures for the several shelf temperatures. The equations for the fitted curves were used to construct a table showing the contents of residual moistures at 300 minute intervals. This table was used for developing successful drying cycles for several concentrations of serum albumin, dilute solutions of interferon, and serum containing HLA antibodies.